1.Methacrylated dermal extracellular matrix hydrogel promotes repair of abdominal wall defects
Zhongyu LIU ; Wenya LI ; Yonghong FAN ; Shuang LYU ; Juan PEI ; Yaqin CHEN ; Beiyu LIU ; Hongyu SUN
Chinese Journal of Tissue Engineering Research 2025;29(10):2074-2082
BACKGROUND:Synthetic polymers,such as polypropylene and polyester,used for the treatment of abdominal wall defects not only lack biodegradability and bioactivity but also fail to meet the demands of complex and irregular wounds.Therefore,finding bioactive materials with low immunogenicity and good histocompatibility has become a hot spot in the repair of abdominal wall defects. OBJECTIVE:To prepare methacryloyl modified dermal extracellular matrix hydrogel and explore its potential application in abdominal wall defect. METHODS:(1)The porcine dermis was acellular with 0.25%trypsin and 1%Triton X-100 in turn to obtain the dermal extracellular matrix.After pepsin digestion and methacrylic anhydride modification,the methacrylated dermal extracellular matrix hydrogel was formed by photocrosslinking.The microscopic morphology of the hydrogel was observed by scanning electron microscope,and its rheological properties,swelling properties and other physical and chemical properties were tested.(2)Mice fibroblasts(L929)were inoculated into methacrylated dermal extracellular matrix hydrogel to detect the cell compatibility.(3)Totally 12 SD rats were randomly divided into two groups(n=6)to create abdominal wall defect model with peritoneum preserved.The defect site of the polypropylene group was filled with polypropylene material,and the hydrogel group was filled with methacrylated dermal extracellular matrix hydrogel.The wound skin of both groups was covered with polypropylene material.The wound healing was observed and histological analysis was carried out. RESULTS AND CONCLUSION:(1)Enzymatic hydrolysis had a good decellularization effect on porcine dermis after decellularization,and the original glycosaminoglycans and collagen were well retained.Scanning electron microscope observation revealed that the dermal extracellular matrix hydrogel presented loose and porous structure.The aperture was between 70 and 120 μm.The swelling ratio was(16.88±3.24)%and the water absorption was(94.24±1.11)%.The rheological property test showed that the methacrylated dermal extracellular matrix hydrogel was stable and had shear thinning characteristics,with injectability.(2)CCK-8 assay and live/dead staining showed that methacrylated dermal extracellular matrix hydrogel had good cell compatibility.(3)The results of animal experiments showed that the skin wound healing rate of the experimental group was higher than that of the control group at 7,10,and 14 days after operation(P<0.05).Hematoxylin-eosin and Masson staining of skin and muscle tissue exhibited that compared with the polypropylene group,the skin wound epithelialization,hair follicle formation,collagen fiber arrangement,and neovascularization were better in the hydrogel group 14 days after surgery.The skin wound new tissue structure was similar to the normal tissue at 28 days after surgery,and scar hyperplasia was less.A small amount of muscle regeneration was observed on day 28 after operation.(4)The results show that the methacrylated dermal extracellular matrix hydrogel can promote wound skin healing and muscle tissue regeneration in rats with abdominal wall defect.
2.Experience and learning curve of single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach
Hongyu CHEN ; Yiyi ZHOU ; Shuai LIN ; Bin XIONG ; Shaoli XIE ; Fang CHEN ; Yuqing KANG ; Qi LYU ; Xiaobo ZHAO
Chinese Journal of Endocrine Surgery 2024;18(1):26-30
Objective:To explore the experience and learning curve of single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach.Methods:Clinical data of 138 patients undergoing single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via oral vestibular approach from Sep. 2019 to Dec. 2021 in the Department of Thyroid and Breast Surgery of Affiliated Hospital of North Sichuan Medical College were retrospectively analyzed. The cumulative sum (CUSUM) method and best-fit curve analysis were used to compare the differences in each index such as operative time, intraoperative bleeding, number of lymph nodes cleared in the central region and postoperative related complications at various stages of the learning curve.Results:All 138 patients underwent single-line suspension rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach, and one patient was converted to open surgery due to large intraoperative bleeding in the mass. There were 14 males and 124 females, mean age (36.07±8.49) years (20-55 years), thyroid tumor size (7.74±6.49) mm (2.4-50mm), 5 cases underwent Subtotal thyroidectomy, 129 cases underwent Unilateral lobectomy + lymph node dissection in the middle region, and 4 cases total thyroidectomy + central zone lymph node dissection. The number of surgical cases corresponding to the apex of the CUSUM learning curve was 45, and the learning curve was divided into two stages: the learning improvement stage (1-45 cases) and the mastery stage (46-138 cases). The operative time, intraoperative bleeding, postoperative hospital stay, and chin numbness were all lower in the proficiency period than in the learning and training period ( P<0.05), and the number of lymph nodes cleared in the central region was larger than that in the learning and improvement stage ( P<0.05), while the differences in other indexes between the two stages were not statistically significant ( P>0.05) . Conclusion:The single-line suspension suction rod-assisted hybrid cavity-building thyroid surgery via the oral vestibular approach has clinical application value and is worth promoting, and the number of surgical cases to be accumulated to master this technique is 45.
3.Effects and mechanism of Setaria italica extract on improving sleep in insomnia mice
Juan WANG ; Chenzi LYU ; Cairong ZHAO ; Hongyu ZHAO ; Zi’ang LI ; Xiang HAN ; Xianglong MENG ; Shuosheng ZHANG
China Pharmacy 2024;35(3):322-326
OBJECTIVE To investigate the effects of Setaria italica extract on improving insomnia model mice and to explore its potential mechanisms. METHODS The mice were randomly assigned into blank group, model group, positive control group (diazepam, 2.6 mg/kg), and S. italica extract low-dose, medium-dose and high-dose groups (1.2, 2.4, 4.8 g/kg), with 10 mice in each group. Except for the blank group, all other groups received intraperitoneal injection of para-chlorophenylalanine (PCPA) to establish the insomnia model. After modeling, the blank group and model group were given a constant volume of normal saline intragastrically, and administration groups were given relevant medicine intragastrically, with a volume of 0.01 mL/g, once a day, for 7 consecutive days. After the administration, the open-field test was conducted to observe the praxiological changes of mice, and to determine the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HTAA) in the hippocampal tissue, as well as the contents of 5-HT, brain-derived neurotrophic factor (BDNF), interleukin-2 (IL-2), IL-6, B-cell lymphoma-2 (Bcl- 2), and Bcl-2-associated X protein (Bax) in the serum. The expression of phosphoinositide 3-kinase/protein kinase B/nuclear factor- κB (PI3K/Akt/NF-κB) signaling pathway related protein was determined in the hippocampus of mice. RESULTS Compared with the model group, the total exercise time of mice in S. italica extract high-dose group was significantly prolonged, but the total rest time was significantly shortened (P<0.01); the number of standing times and modification times were significantly reduced (P< 0.01). The contents of 5-HT, BDNF, and Bcl-2 in serum, and Bcl-2/Bax were significantly increased, while the contents of IL-2, IL-6, and Bax were significantly reduced (P<0.05 or P< 0.01). The content of 5-HTAA in the hippocampal tissue and 202104010910029);the phosphorylation levels of PI3K and Akt proteins were increased significantly, while the phosphorylation level of NF-κB p65 protein was decreased significantly (P<0.05).CONCLUSIONS High-dose of S. italica extract demonstrates significant therapeutic effects on insomnia in mice, and the mechanism of which may be associated with the regulation of PI3K/Akt/NF-κB signaling pathway.
4.Map of benzoapyrene metabolites-DNA adducts in human bronchial epithelial-like cells: Based on chromatin immunoprecipitation followed by sequencing technology
Tingyu JI ; Bin CAO ; Yi LYU ; Xiaomin TONG ; Hongyu SUN ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2024;41(3):323-329
Background The active metabolite of benzo[a]pyrene (BaP), 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), can form adducts with DNA, but the spectrum of BPDE-DNA adducts is unclear. Objective To identify the distribution of BPDE adduct sites and associated genes at the whole-genome level by chromatin immunoprecipitation followed by sequencing (ChIP-Seq), and serve as a basis for further exploring the toxicological mechanisms of BaP. Methods Human bronchial epithelial-like cells (16HBE) were cultured to the fourth generation inthe logarithmic growth phase. Cells were harvested and added to chromatin immunoprecipitation lysis buffer. The lysate was divided into experimental and control groups. The experimental group received a final concentration of 20 μmol·L−1 BPDE solution, while the control group received an equivalent volume of dimethyl sulfoxide solution. The cells were then incubated at 37 °C for 24 h. Chromatin fragments of 100-500 bp were obtained through sonication. BPDE-specific antibody (anti-BPDE 8E11) was used to enrich DNA fragments with BPDE adducts. High-throughput sequencing was conducted to detect BPDE adduct sites. The top 1000 peak sequences were subjected to motif analysis using MEME and DREME software. BPDE adduct target genes at the whole-genome level were annotated, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of BPDE adduct target genes were conducted using bioinformatics techniques. Results The high-throughput sequencing detected a total of 842 BPDE binding sites, distributed across various chromosomes. BPDE covalently bound to both coding and non-coding regions of genes, with 73.9% binding sites located in intergenic regions, 19.6% in intronic regions, and smaller proportions in upstream 2 kilobase, exonic, downstream 2 kilobase, and 5' untranslated regions. Regarding the top 1000 peak sequences, four reliable motifs were identified, revealing that sites rich in adenine (A) and guanine (G) were prone to binding. Through the enrichment analysis of binding sites, a total of 199 BPDE-adduct target genes were identified, with the majority located on chromosomes 1, 5, 7, 12, 17, and X. The GO analysis indicated that these target genes were mainly enriched in nucleic acid and protein binding, participating in the regulation of catalytic activity, transport activity, translation elongation factor activity, and playing important roles in cell division, differentiation, motility, substance transport, and information transfer. The KEGG analysis revealed that these target genes were primarily enriched in pathways related to cardiovascular diseases, cancer, and immune-inflammatory responses. Conclusion Using ChIP-Seq, 199 BPDE adduct target genes at genome-wide level are identified, impacting biological functions such as cell division, differentiation, motility, substance transport, and information transfer. These genes are closely associated with cardiovascular diseases, tumors, and immune-inflammatory responses.
5.7,8-dihydroxy-9,10-epoxybenzoapyrene induced ferroptosis in mouse hippocampal neuron HT22 cells and its mechanism
Xiaohui LI ; Zhaomeng XU ; Hongyu SUN ; Yi LYU ; Xiaomin TONG ; Tingyu JI ; Hui HE ; Jinping ZHENG
Journal of Environmental and Occupational Medicine 2023;40(4):433-440
Background Benzo[a]pyrene (BaP) has neurotoxicity, which can induce the loss of hippocampal neurons in humans and animals and lead to spatial learning and memory dysfunction, but its mechanism is still unclear. Objective To observe the ferroptosis of mouse hippocampal neuron HT22 cells induced by 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), an active metabolite of BaP, and to explore its potential mechanism, so as to provide a basis for the study of BaP neurotoxicity mechanism. Method Mouse hippocampal neuron HT22 cells were selected and divided into four groups: solvent control group and low, medium, and high concentration BPDE exposure groups (0.25, 0.50, and 0.75 μmol·L−1). Cell survival was detected by CCK8 method. Cell morphology and ultrastructure were observed under light and electron microscopes. The levels of reactive oxygen species (ROS) and Fe2+ were detected by fluorescence probe method. Iron, 4-hydroxynonenoic acid (4-HNE), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels were detected with commercial kits. The expression levels of acyl-CoA synthase long chain family member 4 (ACSL4), cyclooxygenase 2 (COX2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were detected by Western blotting. After interventions with ferroptosis inhibitors 20 μmol·L−1 deferoxamine (DFO) and 10 μmol·L−1 ethyl 3-amino-4-cyclohexylaminobenzoate (Fer-1), the cell survival rate of each BPDE exposure group and the changes of the ferroptosis characteristic indicators and protein expression levels were observed. Results With the increase of BPDE concentration, the survival rate of HT22 cells decreased gradually, and the survival rate of each BPDE group was significantly lower than that of the solvent control group (P<0.01). Under light microscope, the number of cells in the high concentration BPDE group was significantly reduced, and atrophic cells and reduced synapses were recorded. Under electron microscope, the HT22 cells in the high concentration BPDE group showed mitochondrial shrinkage, decreased crista, and increased mitochondrial membrane density. Compared with the solvent control group, the levels of intracellular lipid ROS, Fe2+, 4-HNE, and MDA significantly increased in the high concentration group (P<0.01), the GSH and GSH-PX levels were significantly decreased (P<0.01), the protein expression levels of ASCL4 and COX2 were significantly increased (P<0.01), and the protein expression levels of SCL7A11 and GPX4 were significantly decreased (P<0.01). The ferroptosis inhibitors DFO and Fer-1 significantly reversed the cell survival rate (P<0.01), the ferroptosis characteristic indicators (ROS, Fe2+, 4-HNE, MDA, GSH, and GSH-PX levels) (P<0.01), and the expression levels of ferroptosis-related proteins (ACSL4, COX2, SLC7A11, and GPX4) (P<0.01) in the high concentration BPDE group. Conclusion BPDE can induce ferroptosis in mouse hippocampal neuron HT22 cells, which may be related to the inhibition of SLC7A11/GSH/GPX4 axis and the induction of iron metabolism disorder.
6.Clinical report of two dose fractionation modes using carbon ion beam therapy in the lymph node drainage area for lung cancer
Xin PAN ; Yihe ZHANG ; Xiaojun LI ; Tong MA ; Xin WANG ; Yuling YANG ; Hongyu CHAI ; Tianyan QIN ; Caixia LYU ; Pengqing LI ; Yancheng YE ; Yanshan ZHANG
Chinese Journal of Radiation Oncology 2023;32(3):215-221
Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.
7.Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism
Yinglan LYU ; Long CHENG ; Lu SHI ; Hongyu DAI ; Yuhui DUAN ; Yongcheng AN ; Huimin LI ; Chen WANG ; Changhao HE ; Yan HUANG ; Huilin ZHANG ; Wanxin FU ; Yanyan MENG ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):137-143
ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 (CCK-8) assay was used to detect the effect of different concentration of rutin (3.125, 6.25, 12.5, 25, 50, 100, 200 μmol·L-1) on 3T3-L1 cell activity, and Western blot to examine the effect of rutin (12.5, 25, 50 μmol·L-1) on the expression of thermogenesis-associated proteins uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in adipocytes. After the optimal concentration of rutin was determined, the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining, and the expression of nuclear respiratory factor 1 (NRF1), nuclear respiratory factor 2 (NRF2) and mitochondrial transcription factor A (TFAM), which were the landmark proteins of mitochondrial biosynthesis, was detected by Western blot. ResultCompared with the blank group, 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity (P<0.01). Compared with the blank group, at the concentration of 12.5, 25, 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins (UCP1, PRDM16, and PGC-1α) (P<0.01), which was determined as the optimal concentration. Compared with the blank group, 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells (P<0.01) and the expression of the markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM) (P<0.01). In addition, 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes (P<0.01). ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins (UCP1, PRDM16, and PGC-1α) and markers of mitochondrial biosynthesis (NRF1, NRF2, and TFAM), thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.
8.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
9.Enriched rehabilitation improves dual-task gait disorder after a transient ischemic attack
Xin WANG ; Yifeng QUAN ; Xiaojia TANG ; Hongyu ZHOU ; Yicheng LYU ; Nan SHI ; Pin YAN ; Junya WANG
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(5):402-406
Objective:To observe the effect of enriched rehabilitation on dual-task gait disorder after a transient ischemic attack (TIA) and explore its mechanism.Methods:Sixty TIA patients were randomly divided into a control group and an observation group, each of 30. Another 30 healthy counterparts were selected to form a healthy control group. All of the TIA patients were given routine medication to lower blood pressure and improve brain function, while the observation group was additionally provided with enriched rehabilitation training for 12 weeks. Before and after the intervention, the gait and cognitive functioning of all of the subjects were quantified and their event-related potentials (P300s) and serum brain-derived neurotrophic factor (BDNF) levels were also measured.Results:Before the treatment there were significant differences between the TIA groups and healthy controls in all of the measurements, but there were no significant differences between the control and observation groups. After the treatment, no significant improvement was observed in any of the control group′s results, but there was significant improvement in the observation group′s gait parameters, cognitive functioning, average serum BDNF concentration and in the average latency and amplitude of its P300 signals.Conclusions:Enriched rehabilitation can improve the gait of TIA patients, perhaps through increasing their serum BDNF concentration and improving their cognition.
10.TGF-β-related Signaling Pathways in Pathogenesis of Diabetes and Prospect of Chinese Medicine Intervention: A Review
Chen WANG ; Long CHENG ; Lu SHI ; Changhao HE ; Yongcheng AN ; Yuhui DUAN ; Hongyu DAI ; Huimin LI ; Yinglan LYU ; Wanxin FU ; Yan HUANG ; Huilin ZHANG ; Baosheng ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):254-263
The incidence of diabetes has been on the rise as the result of lifestyle changes, especially the high-fat diet and reduced exercise. Thus, it has become a global public health problem and it is an urgent task to explore effective therapy. There has been an explosion of research on the relationship of transforming growth factor-β (TGF-β) signaling pathways with diabetes complications and tumors, but the role of the pathways in the occurrence and progression of diabetes remains unclear. TGF-β signaling pathways can be activated by many factors, directly or indirectly leading to the apoptosis of islet β cells and insulin resistance (IR), and thus they are expected to become new targets for the treatment of diabetes. TGF-β-related signaling pathways involve AMP-activated proteinkinase (AMPK), protooncogene (c-Myc), Ski-relatednovel protein N (SnoN), Smad ubiquitination regulatory factor 1 (Smurf1), miR-335-5p, and other signaling molecules. They participate in the occurrence and development of IR, apoptosis of islet β cells, insulin secretion disorder, fibrosis of adipocytes, and metabolic disorder of adipocytes, and inhibit the browning of white adipose tissue, playing an important part in the pathological process of human diabetes. According to traditional Chinese medicine (TCM), the pathogenesis of diabetes is the deficiency of Qi and Yin, and the late stage is characterized by the syndrome of Qi deficiency, and Yang deficiency and blood stasis, which should be treated according to the principle of replenishing Qi and nourishing Yin, warming Yang and activating blood. It has been found that the efficacy of some Chinese medicinals and compound prescriptions on diabetes is closely related to the TGF-β signaling pathways. This paper reviews TGF-β-associated signaling pathways, elucidating the roles of them in pathogenesis of diabetes, and analyzes the relationship of TGF-β-associated signaling pathways with the effect of compound Chinese medicine prescriptions against diabetes. This study is expected to lay a theoretical basis for the research on the treatment diabetes.

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